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Treating Patients With Germline BRCA-Mutated, Her2-Negative Metastatic Breast Cancer |
Practice Community
Arlington, VA
Practice Niche
Breast Cancer
Hospital and Institutional Affiliations
Virginia Cancer Specialists, The US Oncology Network
Question What are your thoughts about the use of poly([ADP]–ribose) polymerase (PARP) inhibitors in the adjuvant setting in BRCA-mutated, HER2-negative disease? |
Answer In the early adjuvant breast cancer setting there is a large phase 3 randomized study, OlympiA, (ClinicalTrials.gov Identifier: NCT02032823) that has now closed to accrual. We are anxiously awaiting the results to see if PARP inhibitors improve outcomes in early breast cancer as they do in BRCA-mutated metastatic disease. |
Question How do you think germline mutations in the homologous recombination pathway genes could contribute to PARP inhibitor sensitivity, if at all? |
Answer Homologous recombination seems to be a predictor of response to DNA-damaging agents such as PARP inhibitors in ovarian cancer. BRCA-mutated cells have defects in the homologous recombination pathway but can also have deficiencies through other avenues. More trials are needed to see how homologous recombination can predict sensitivity to PARP in breast cancer. |
Question The addition of veliparib to carboplatin/paclitaxel in BROCADE3 (ClinicalTrials.gov Identifier: NCT02163694) significantly improved progression-free survival (PFS), but not overall survival (OS). What do you make of these seemingly discordant survival findings? |
Answer Historically, in metastatic breast cancer, we have not always seen significant benefits in overall survival. Exceptions where we have seen significant overall survival benefit is with trastuzumab and, more recently, with cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors. For a long time, studies of CDK 4/6 inhibitors also only showed a progression-free survival benefit. |
Question Extended follow-up for OlympiAD showed that OS did not differ significantly between the treatment arms studied, but that there was an OS benefit that was “suggested” by the data. What does this really mean for patients? |
Answer The same applies here as the BROCADE3 trial. The data signal that these drugs are active. We often don’t see a stunning overall survival benefit, partly due to follow-up. What we do know from OlympiAD data and EMBRACA data is that single-agent PARP inhibitors are very active in this population. We can potentially spare patients some toxicity and give single-agent PARP inhibitors alone. |
Question There was a recent warning from the US Food and Drug Administration that cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors could cause interstitial lung disease (ILD) and pneumonitis in select breast cancer patient groups. Would this warning influence your prescribing practices? |
Answer Interstitial lung disease and pneumonitis are significant toxicities associated with many antineoplastic therapies including paclitaxel and everolimus. Because of the significant benefit noted with palbociclib, ribociclib, and abemaciclib, we will continue to prescribe CDK 4/6 inhibitors, but appropriately monitor for pneumonitis as we do other toxicities. |
Question A recent study presentation1 found that the use of breast radiotherapy (as therapy and prevention) should be considered safe in the gBRCA population as it relates to secondary malignancies. What factors would likely influence the decision to administer radiotherapy? |
Answer Looking at this study it is important to remember that the data reflect a population of patients that started treatment as far back as 1991. Additionally, it was a small study with only 230 women. |
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